A modified LC‐MS/MS method for determination of tetramethylpyrazine in microdialysis samples and calibration of home‐made linear probes

Han, Jinzhao; Jun, Sun Hee; Liu, Jiyong; Jin-hong, HU; Chen, Fang

doi:10.1002/bmc.2689

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…Ligustrazine ( Fig. 1), also known as 2,3,5,6-tetramethylpyrozine (TMP), is one of the most important active ingredients of Chuan Xiong (5). The compound can penetrate BBB and can be found throughout the brain.…”

Section: Introductionmentioning

confidence: 99%

Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion

Tan

Cheng

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Ligustrazine, also known as 2,3,5,6-tetramethylpyrazine (TMP), one of the major active compounds of Ligusticum wallichii Franchat., has been shown to reduce neuroinflammation and protect neurons during cerebral ischemia/reperfusion injury. However, whether it reduces blood-brain barrier (BBB) permeability during ischemic stroke is unclear. The aim of the present study was to investigate the role that TMP plays in protecting the BBB integrity in ischemia/reperfusion injury and to investigate the relevant mechanisms involved. Rats received an intraperitoneal injection of 20 mg/kg TMP 15 min before the onset of ischemia, which was induced by middle cerebral artery occlusion. Infarct volume, neurological score, brain edema, BBB permeability and tight junction protein impairment were observed. The results showed that TMP reduced the neurological score and levels of brain infarction and edema. In addition, TMP significantly decreased BBB permeability and prevented the impairment of occludin and claudin-5, two tight junction protein components of the BBB, in rat brains with ischemia/reperfusion injury. In addition, the expression and activity of matrix metalloproteinases, enzymes responsible for the degradation of the extracellular matrix and tight junctions, were reduced in the rat brains by TMP treatment. These results combined suggest that TMP reduces BBB permeability as well as neuronal damage in focal cerebral ischemia/reperfusion injury in rats.

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Section: Introductionmentioning

confidence: 99%

Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion

Tan

Cheng

et al. 2015

Experimental and Therapeutic Medicine

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“…Various pyrazines can be synthesized both chemically and biologically, including tetramethylpyrazine (TTMP), which is produced by different bacteria (1,2) or plants (3,4). However, there is very little information available on the biodegradation of these N-heterocyclic compounds.…”

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confidence: 99%

Identification and Characterization of a Tetramethylpyrazine Catabolic Pathway in Rhodococcus jostii TMP1

Kutanovas

Stankevičiūtė

Urbelis

et al. 2013

Appl Environ Microbiol

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bAt present, there are no published data on catabolic pathways of N-heterocyclic compounds, in which all carbon atoms carry a substituent. We identified the genetic locus and characterized key reactions in the aerobic degradation of tetramethylpyrazine in Rhodococcus jostii strain TMP1. By comparing protein expression profiles, we identified a tetramethylpyrazine-inducible protein of 40 kDa and determined its identity by tandem mass spectrometry (MS-MS) de novo sequencing. Searches against an R. jostii TMP1 genome database allowed the identification of the tetramethylpyrazine-inducible protein-coding gene. The tetramethylpyrazine-inducible gene was located within a 13-kb genome cluster, denominated the tetramethylpyrazine degradation (tpd) locus, that encoded eight proteins involved in tetramethylpyrazine catabolism. The genes from this cluster were cloned and transferred into tetramethylpyrazine-nondegrading Rhodococcus erythropolis strain SQ1. This allowed us to verify the function of the tpd locus, to isolate intermediate metabolites, and to reconstruct the catabolic pathway of tetramethylpyrazine. We report that the degradation of tetramethylpyrazine is a multistep process that includes initial oxidative aromatic-ring cleavage by tetramethylpyrazine oxygenase, TpdAB; subsequent hydrolysis by (Z)-N,N=-(but-2-ene-2,3-diyl)diacetamide hydrolase, TpdC; and further intermediate metabolite reduction by aminoalcohol dehydrogenase, TpdE. Thus, the genes responsible for bacterial degradation of pyrazines have been identified, and intermediate metabolites of tetramethylpyrazine degradation have been isolated for the first time. P yrazines, monocyclic aromatic rings with two nitrogen atoms in para position, are a class of compounds that occur almost ubiquitously in nature. Various pyrazines can be synthesized both chemically and biologically, including tetramethylpyrazine (TTMP), which is produced by different bacteria (1, 2) or plants (3, 4). However, there is very little information available on the biodegradation of these N-heterocyclic compounds. While bacterial strains able to use various alkyl-substituted pyrazines as a sole carbon and energy source have been isolated and described (5-9), almost nothing is known about the degradation pathways of alkylpyrazines, including tetramethylpyrazine, in which all carbon atoms carry a substituent.Under aerobic conditions, alkylated pyrazines are metabolized via oxidative degradation, leading to the hydroxylation of the ring at a free position. Rhodococcus erythropolis DSM 6138 and Arthrobacter sp. strain DSM 6137 can use 2,5-dimethylpyrazine as a source of carbon and energy. The catabolism of 2,5-dimethylpyrazine by these microorganisms gives rise to the intermediate metabolite 2-hydroxy-3,6-dimethylpyrazine, which accumulates in the medium, indicating that ring hydroxylation occurs during the initial steps of degradation (5). However, no enzymes involved in this bioconversion were reported in the patent that describes the aforementioned reactions (5).The 2,5-dimethylpyraz...

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“…The in vitro recovery by gain (R gain ) during dialysis calculated using the following equation [34,35] : The drug-free aCSF was perfused through the probe at 1.5 μL/min and the microdialysate samples were collected.…”

Section: Calibration Of the Microdialysis Probesmentioning

confidence: 99%

“…The in vitro recovery by loss (R loss ) was calculated according to the following equation [34][35][36][37] : Recovery by loss of the analytes from the probe during retrodialysis examined using the same probes (n = 3) and flow rates (1.5 μL/min), which were perfused with the drug-spiked aCSF solutions at three concentration levels (3, 20, and 400 ng/mL for tramadol and 1, 5, and 40 ng/mL for ODT) and immersed with drug-free aCSF solutions.…”

Section: Calibration Of the Microdialysis Probesmentioning

confidence: 99%

Intracerebral microdialysis coupled to LC–MS/MS for the determination tramadol and its major pharmacologically active metabolite O‐desmethyltramadol in rat brain microdialysates

Liu

Wang

et al. 2017

Drug Testing and Analysis

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A rapid and sensitive method involving liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) coupled to an intracerebral microdialysis technique was developed for the determination and pharmacokinetic investigation of tramadol and its major active metabolite O-desmethyltramadol (ODT) in rat brain. The microdialysis samples were separated on a C18 column and eluted with a mobile phase of acetonitrile-water-formic acid (50:50:0.1; v/v/v) at a flow rate of 0.3 mL/min. The ESI-MS/MS spectra were performed in electrospray positive ion mode, and the analytes were detected by multiple reaction monitoring (MRM) of the transitions m/z [M + H] 264.3 → 58.2 for tramadol, m/z [M + H] 250.3 → 58.3 for ODT, and m/z [M + H] 379.4 → 264.0 for ambroxol (internal standard; IS). The total run time was 4.0 min. A lower limit of quantitation (LLOQ) was achieved as 1 ng/mL for tramadol and 0.5 ng/mL for ODT, with excellent linearity over a concentration range of 1 ~ 500 ng/mL (r > 0.99) for tramadol and 0.5 ~ 50 ng/mL for ODT (r > 0.99), respectively. The proposed method was successfully applied to the pharmacokinetic studies of tramadol and ODT in rat brain. Copyright © 2017 John Wiley & Sons, Ltd.

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A modified LC‐MS/MS method for determination of tetramethylpyrazine in microdialysis samples and calibration of home‐made linear probes

Cited by 12 publications

References 22 publications

Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion

Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion

Identification and Characterization of a Tetramethylpyrazine Catabolic Pathway in Rhodococcus jostii TMP1

Intracerebral microdialysis coupled to LC–MS/MS for the determination tramadol and its major pharmacologically active metabolite O‐desmethyltramadol in rat brain microdialysates

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